A Comprehensive Oral Health Research Center of Discovery (COHRCD) is proposed at the University of California, San Francisco (UCSF) to serve San Francisco and Northern California. The scientific theme of this COHRCD is "New Strategies for Enhancing Tissue Integrity and Repair." This theme will be pursued from two complementary points of view: enhancing the repair of oral and craniofacial tissues with developmental or acquired defects: and intervening to prevent the destruction and degeneration of these tissues. This theme has relevance for children born with craniofacial anomalies; young children at risk for rampant caries; people with facial trauma, oral cancer, severe periodontitis and temporomandibular joint disorders; and patients with chronic disabling skeletal disorders, including alveolar bone loss and tooth loss, osteoarthritis and osteoporosis. Regarding enhancement of tissue repair, our hypothesis is that the processes of normal tissue differentiation and maturation, and of successful tissue remodeling and repair, share important mechanistic features. This idea underlies our desire to study these processes together in an integrated program so as to uncover novel markers of normal development and function, and novel strategies for stimulating regenerative repair of connective and skeletal tissues. Regarding maintenance of tissue integrity, aggressive diagnostic, interventional and educational outreach strategies to reduce the incidence and morbidity of chronic degenerative diseases and disorders are proposed. The specific aims of this COHRCD are to: 1) Support basic and patient-oriented research projects that address mechanisms of development and repair of connective and skeletal tissues. 2) Support clinical (patient-oriented) research related to the maintenance of tissue integrity and prevention of diseases, disorders and behaviors that result in tissue destruction. 3) Establish core facilities to provide technical services and resources to COHRCD-affiliated projects. 5) Provide an enriched environment for training future health-care professionals and scientists. 6) Establish mechanisms, including the Bay Area Tissue Engineering and Repair Network (BayTERN) and the Millberry Seminars program, to increase communication among investigators in COHRCD-supported projects and between investigators and regional industry, area health-care providers and community institutions in the Norther California region.